Migraine ICYMI

Key clinical point: Survey findings from a real-world tertiary headache clinic support the efficacy and safety of ubrogepant for acute treatment of migraine.

Major finding: Complete headache freedom and headache relief at 2 hours after taking ubrogepant for at least 75% of treated attacks were achieved in 19.0% and 47.6% of patients with migraine, respectively. Overall, 31.1% of patients reported being very satisfied with ubrogepant. Rates of adverse events were higher than those observed in clinical trials. However, no severe/serious adverse events were reported.

Study details: The data come from an analysis of questionnaire responses of 106 adult patients with migraine with or without aura treated with ubrogepant at a tertiary headache center.

Disclosures: No source of funding was declared. DW Dodick declared research support/consulting from various sources. AJ Starling declared consulting fees from Alder, Allergan, Amgen, Axsome Therapeutics, and others. Four of the other authors had no disclosures.

Source: Chiang C-C et al. Headache. 2021 Feb 5. doi: 10.1111/head.14062.

Key clinical point: Survey findings from a real-world tertiary headache clinic support the efficacy and safety of ubrogepant for acute treatment of migraine.

Major finding: Complete headache freedom and headache relief at 2 hours after taking ubrogepant for at least 75% of treated attacks were achieved in 19.0% and 47.6% of patients with migraine, respectively. Overall, 31.1% of patients reported being very satisfied with ubrogepant. Rates of adverse events were higher than those observed in clinical trials. However, no severe/serious adverse events were reported.

Study details: The data come from an analysis of questionnaire responses of 106 adult patients with migraine with or without aura treated with ubrogepant at a tertiary headache center.

Disclosures: No source of funding was declared. DW Dodick declared research support/consulting from various sources. AJ Starling declared consulting fees from Alder, Allergan, Amgen, Axsome Therapeutics, and others. Four of the other authors had no disclosures.

Source: Chiang C-C et al. Headache. 2021 Feb 5. doi: 10.1111/head.14062.

Key clinical point: Survey findings from a real-world tertiary headache clinic support the efficacy and safety of ubrogepant for acute treatment of migraine.

Major finding: Complete headache freedom and headache relief at 2 hours after taking ubrogepant for at least 75% of treated attacks were achieved in 19.0% and 47.6% of patients with migraine, respectively. Overall, 31.1% of patients reported being very satisfied with ubrogepant. Rates of adverse events were higher than those observed in clinical trials. However, no severe/serious adverse events were reported.

Study details: The data come from an analysis of questionnaire responses of 106 adult patients with migraine with or without aura treated with ubrogepant at a tertiary headache center.

Disclosures: No source of funding was declared. DW Dodick declared research support/consulting from various sources. AJ Starling declared consulting fees from Alder, Allergan, Amgen, Axsome Therapeutics, and others. Four of the other authors had no disclosures.

Source: Chiang C-C et al. Headache. 2021 Feb 5. doi: 10.1111/head.14062.

Key clinical point: Inadequate magnesium consumption through the diet is associated with migraine in US adults, aged 20-50 years.

Major finding: Only 26.1% of participants with migraine met their recommended dietary allowance (RDA) for magnesium through diet and supplements. Attainment of the RDA for magnesium through diet and supplements was associated with lower odds of migraine (adjusted odds ratio, 0.83; P = .035).

Study details: An analysis of cross-sectional data of 3,626 individuals aged 20-50 years from the National Health and Nutrition Examination Survey (2001-2004) who were categorized into migraine (n=905) and control (n=2,721) groups.

 Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.

Source: Slavin M et al. Headache. 2021 Jan 27. doi: 10.1111/head.14065.

Key clinical point: Inadequate magnesium consumption through the diet is associated with migraine in US adults, aged 20-50 years.

Major finding: Only 26.1% of participants with migraine met their recommended dietary allowance (RDA) for magnesium through diet and supplements. Attainment of the RDA for magnesium through diet and supplements was associated with lower odds of migraine (adjusted odds ratio, 0.83; P = .035).

Study details: An analysis of cross-sectional data of 3,626 individuals aged 20-50 years from the National Health and Nutrition Examination Survey (2001-2004) who were categorized into migraine (n=905) and control (n=2,721) groups.

 Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.

Source: Slavin M et al. Headache. 2021 Jan 27. doi: 10.1111/head.14065.

Key clinical point: Inadequate magnesium consumption through the diet is associated with migraine in US adults, aged 20-50 years.

Major finding: Only 26.1% of participants with migraine met their recommended dietary allowance (RDA) for magnesium through diet and supplements. Attainment of the RDA for magnesium through diet and supplements was associated with lower odds of migraine (adjusted odds ratio, 0.83; P = .035).

Study details: An analysis of cross-sectional data of 3,626 individuals aged 20-50 years from the National Health and Nutrition Examination Survey (2001-2004) who were categorized into migraine (n=905) and control (n=2,721) groups.

 Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.

Source: Slavin M et al. Headache. 2021 Jan 27. doi: 10.1111/head.14065.

Key clinical point: Percutaneous patent foramen ovale (PFO) closure with the Amplatzer PFO Occluder significantly reduced migraine days and attacks in patients with episodic migraine who had PFO and were refractory to preventive medical therapy.

Major finding: At 12 months, PFO closure vs. medical therapy group showed a significantly greater mean reduction in monthly migraine days (−3.1 vs. −1.9 days; P = .02) and the number of monthly migraine attacks (−2.0 vs. −1.4; P = .01). Rate of complete migraine cessation was significantly higher in PFO closure vs. medical therapy (9% vs. 0.7%; P less than .001) group. No clinically relevant adverse events were reported.

Study details: Findings are from individual patient-level data from 2 randomized migraine trials PRIMA and PREMIUM involving 337 patients with episodic migraine and PFO randomly allocated to either PFO closure+medical therapy (n=176) or medical therapy alone (n=161).

Disclosures: The study did not receive any funding. Dr. AC Charles, Dr. S Sorensen, Dr. SD Silberstein and Dr. JM Tobis were on the steering committee for the PREMIUM trial. Dr. HP Mattle and Dr. B Meier were on the steering committee for the PRIMA trial.  Dr. B West, Dr. B Meier and Dr. JM Tobis declared receiving funds, serving as proctor/speaker/consultant for various sources. All other authors declared no conflicts of interest.

Source: Mojadidi MK et al. J Am Coll Cardiol. 2021 Feb 16. doi: 10.1016/j.jacc.2020.11.068.

Key clinical point: Percutaneous patent foramen ovale (PFO) closure with the Amplatzer PFO Occluder significantly reduced migraine days and attacks in patients with episodic migraine who had PFO and were refractory to preventive medical therapy.

Major finding: At 12 months, PFO closure vs. medical therapy group showed a significantly greater mean reduction in monthly migraine days (−3.1 vs. −1.9 days; P = .02) and the number of monthly migraine attacks (−2.0 vs. −1.4; P = .01). Rate of complete migraine cessation was significantly higher in PFO closure vs. medical therapy (9% vs. 0.7%; P less than .001) group. No clinically relevant adverse events were reported.

Study details: Findings are from individual patient-level data from 2 randomized migraine trials PRIMA and PREMIUM involving 337 patients with episodic migraine and PFO randomly allocated to either PFO closure+medical therapy (n=176) or medical therapy alone (n=161).

Disclosures: The study did not receive any funding. Dr. AC Charles, Dr. S Sorensen, Dr. SD Silberstein and Dr. JM Tobis were on the steering committee for the PREMIUM trial. Dr. HP Mattle and Dr. B Meier were on the steering committee for the PRIMA trial.  Dr. B West, Dr. B Meier and Dr. JM Tobis declared receiving funds, serving as proctor/speaker/consultant for various sources. All other authors declared no conflicts of interest.

Source: Mojadidi MK et al. J Am Coll Cardiol. 2021 Feb 16. doi: 10.1016/j.jacc.2020.11.068.

Key clinical point: Percutaneous patent foramen ovale (PFO) closure with the Amplatzer PFO Occluder significantly reduced migraine days and attacks in patients with episodic migraine who had PFO and were refractory to preventive medical therapy.

Major finding: At 12 months, PFO closure vs. medical therapy group showed a significantly greater mean reduction in monthly migraine days (−3.1 vs. −1.9 days; P = .02) and the number of monthly migraine attacks (−2.0 vs. −1.4; P = .01). Rate of complete migraine cessation was significantly higher in PFO closure vs. medical therapy (9% vs. 0.7%; P less than .001) group. No clinically relevant adverse events were reported.

Study details: Findings are from individual patient-level data from 2 randomized migraine trials PRIMA and PREMIUM involving 337 patients with episodic migraine and PFO randomly allocated to either PFO closure+medical therapy (n=176) or medical therapy alone (n=161).

Disclosures: The study did not receive any funding. Dr. AC Charles, Dr. S Sorensen, Dr. SD Silberstein and Dr. JM Tobis were on the steering committee for the PREMIUM trial. Dr. HP Mattle and Dr. B Meier were on the steering committee for the PRIMA trial.  Dr. B West, Dr. B Meier and Dr. JM Tobis declared receiving funds, serving as proctor/speaker/consultant for various sources. All other authors declared no conflicts of interest.

Source: Mojadidi MK et al. J Am Coll Cardiol. 2021 Feb 16. doi: 10.1016/j.jacc.2020.11.068.

Poor adherence and high discontinuance rates frequently compromise achieving optimal triptan therapy in managing acute migraine headaches, a new Danish study shows.

“Few people continue on triptans either due to lack of efficacy or too many adverse events,” said Alan Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles. “Some people overuse triptans when they are available and work well, but the patients are not properly informed, and do not listen.”

Migraine headaches fall among some of the most common neurologic disorders and claims the No. 2 spot in diseases that contribute to life lived with disability. An estimated 11.7% have migraine episodes annually, and the disorder carries a high prevalence through the duration of the patient’s life.

Triptans were noted as being a highly effective solution for acute migraine management when they were first introduced in the early 1990s and still remain the first-line treatment for acute migraine management not adequately controlled by ordinary analgesics and NSAIDs. As a drug class, the side-effect profile of triptans can vary, but frequent users run the risk of medication overuse headache, a condition noted by migraines of increased frequency and intensity.
 

25 years of triptan use

Study investigators conducted a nationwide, register-based cohort study using data collected from 7,435,758 Danish residents who accessed the public health care system between Jan. 1, 1994, and Oct. 31, 2019. The time frame accounts for a period of 139.0 million person-years when the residents were both alive and living in Denmark. Their findings were published online Feb. 14, 2021, in Cephalalgia.

Researchers evaluated and summarized purchases of all triptans in all dosage forms sold in Denmark during that time frame. These were sumatriptan, naratriptan, zolmitriptan, rizatriptan, almotriptan, eletriptan, and frovatriptan. Based on their finding, 381,695 patients purchased triptans at least one time. Triptan users were more likely to be female (75.7%) than male (24.3%).

Dr. Rapoport, who was not involved in the study, feels the differences in use between genders extrapolate to the U.S. migraine population as well. “Three times more women have migraines than men and buy triptans in that ratio,” he said.

Any patient who purchased at least one of any triptan at any point during the course of the study was classified as a triptan user. Triptan overuse is defined as using a triptan greater for at least 10 days a month for 3 consecutive months, as defined by the International Classification of Headache Disorders. It’s important to note that triptan are prescribed to patients for only two indications – migraines and cluster headaches. However, cluster headaches are extremely rare.

The study’s investigators summarized data collected throughout Denmark for more than a quarter of a century. The findings show an increase in triptan use from 345 defined daily doses to 945 defined daily doses per 1,000 residents per year along with an increased prevalence on triptan use from 5.17 to 14.57 per 1,000 inhabitants. In addition, 12.3% of the Danish residents who had migraines bought a triptan between 2014 and 2019 – data Dr. Rapoport noted falls in lines with trends in other Western countries, which range between 12% and 13%.

Nearly half of the first-time triptan buyers (43%) did not purchase another triptan for 5 years. In conflict with established guidelines, 90% of patients that discontinued triptan-based treatment had tried only one triptan type.

One important factor contributing to the ease of data collection is that the Danish population has free health care, coupled with sizable reimbursements for their spending. The country’s accessible health care system negates the effects of barriers related to price and availability while engendering data that more accurately reflects the patients’ experience based on treatment need and satisfaction.

“In a cohort with access to free clinical consultations and low medication costs, we observed low rates of triptan adherence, likely due to disappointing efficacy and/or unpleasant side effects rather than economic considerations. Triptan success continues to be hindered by poor implementation of clinical guidelines and high rates of treatment discontinuance,” the researchers concluded.

“The most surprising thing about this study is it is exactly what I would have expected if triptans in the U.S. were free,” Dr. Rapoport said.

Dr. Rapoport is the editor in chief of Neurology Reviews and serves as a consultant to several pharmaceutical companies.

Poor adherence and high discontinuance rates frequently compromise achieving optimal triptan therapy in managing acute migraine headaches, a new Danish study shows.

“Few people continue on triptans either due to lack of efficacy or too many adverse events,” said Alan Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles. “Some people overuse triptans when they are available and work well, but the patients are not properly informed, and do not listen.”

Migraine headaches fall among some of the most common neurologic disorders and claims the No. 2 spot in diseases that contribute to life lived with disability. An estimated 11.7% have migraine episodes annually, and the disorder carries a high prevalence through the duration of the patient’s life.

Triptans were noted as being a highly effective solution for acute migraine management when they were first introduced in the early 1990s and still remain the first-line treatment for acute migraine management not adequately controlled by ordinary analgesics and NSAIDs. As a drug class, the side-effect profile of triptans can vary, but frequent users run the risk of medication overuse headache, a condition noted by migraines of increased frequency and intensity.
 

25 years of triptan use

Study investigators conducted a nationwide, register-based cohort study using data collected from 7,435,758 Danish residents who accessed the public health care system between Jan. 1, 1994, and Oct. 31, 2019. The time frame accounts for a period of 139.0 million person-years when the residents were both alive and living in Denmark. Their findings were published online Feb. 14, 2021, in Cephalalgia.

Researchers evaluated and summarized purchases of all triptans in all dosage forms sold in Denmark during that time frame. These were sumatriptan, naratriptan, zolmitriptan, rizatriptan, almotriptan, eletriptan, and frovatriptan. Based on their finding, 381,695 patients purchased triptans at least one time. Triptan users were more likely to be female (75.7%) than male (24.3%).

Dr. Rapoport, who was not involved in the study, feels the differences in use between genders extrapolate to the U.S. migraine population as well. “Three times more women have migraines than men and buy triptans in that ratio,” he said.

Any patient who purchased at least one of any triptan at any point during the course of the study was classified as a triptan user. Triptan overuse is defined as using a triptan greater for at least 10 days a month for 3 consecutive months, as defined by the International Classification of Headache Disorders. It’s important to note that triptan are prescribed to patients for only two indications – migraines and cluster headaches. However, cluster headaches are extremely rare.

The study’s investigators summarized data collected throughout Denmark for more than a quarter of a century. The findings show an increase in triptan use from 345 defined daily doses to 945 defined daily doses per 1,000 residents per year along with an increased prevalence on triptan use from 5.17 to 14.57 per 1,000 inhabitants. In addition, 12.3% of the Danish residents who had migraines bought a triptan between 2014 and 2019 – data Dr. Rapoport noted falls in lines with trends in other Western countries, which range between 12% and 13%.

Nearly half of the first-time triptan buyers (43%) did not purchase another triptan for 5 years. In conflict with established guidelines, 90% of patients that discontinued triptan-based treatment had tried only one triptan type.

One important factor contributing to the ease of data collection is that the Danish population has free health care, coupled with sizable reimbursements for their spending. The country’s accessible health care system negates the effects of barriers related to price and availability while engendering data that more accurately reflects the patients’ experience based on treatment need and satisfaction.

“In a cohort with access to free clinical consultations and low medication costs, we observed low rates of triptan adherence, likely due to disappointing efficacy and/or unpleasant side effects rather than economic considerations. Triptan success continues to be hindered by poor implementation of clinical guidelines and high rates of treatment discontinuance,” the researchers concluded.

“The most surprising thing about this study is it is exactly what I would have expected if triptans in the U.S. were free,” Dr. Rapoport said.

Dr. Rapoport is the editor in chief of Neurology Reviews and serves as a consultant to several pharmaceutical companies.

Poor adherence and high discontinuance rates frequently compromise achieving optimal triptan therapy in managing acute migraine headaches, a new Danish study shows.

“Few people continue on triptans either due to lack of efficacy or too many adverse events,” said Alan Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles. “Some people overuse triptans when they are available and work well, but the patients are not properly informed, and do not listen.”

Migraine headaches fall among some of the most common neurologic disorders and claims the No. 2 spot in diseases that contribute to life lived with disability. An estimated 11.7% have migraine episodes annually, and the disorder carries a high prevalence through the duration of the patient’s life.

Triptans were noted as being a highly effective solution for acute migraine management when they were first introduced in the early 1990s and still remain the first-line treatment for acute migraine management not adequately controlled by ordinary analgesics and NSAIDs. As a drug class, the side-effect profile of triptans can vary, but frequent users run the risk of medication overuse headache, a condition noted by migraines of increased frequency and intensity.
 

25 years of triptan use

Study investigators conducted a nationwide, register-based cohort study using data collected from 7,435,758 Danish residents who accessed the public health care system between Jan. 1, 1994, and Oct. 31, 2019. The time frame accounts for a period of 139.0 million person-years when the residents were both alive and living in Denmark. Their findings were published online Feb. 14, 2021, in Cephalalgia.

Researchers evaluated and summarized purchases of all triptans in all dosage forms sold in Denmark during that time frame. These were sumatriptan, naratriptan, zolmitriptan, rizatriptan, almotriptan, eletriptan, and frovatriptan. Based on their finding, 381,695 patients purchased triptans at least one time. Triptan users were more likely to be female (75.7%) than male (24.3%).

Dr. Rapoport, who was not involved in the study, feels the differences in use between genders extrapolate to the U.S. migraine population as well. “Three times more women have migraines than men and buy triptans in that ratio,” he said.

Any patient who purchased at least one of any triptan at any point during the course of the study was classified as a triptan user. Triptan overuse is defined as using a triptan greater for at least 10 days a month for 3 consecutive months, as defined by the International Classification of Headache Disorders. It’s important to note that triptan are prescribed to patients for only two indications – migraines and cluster headaches. However, cluster headaches are extremely rare.

The study’s investigators summarized data collected throughout Denmark for more than a quarter of a century. The findings show an increase in triptan use from 345 defined daily doses to 945 defined daily doses per 1,000 residents per year along with an increased prevalence on triptan use from 5.17 to 14.57 per 1,000 inhabitants. In addition, 12.3% of the Danish residents who had migraines bought a triptan between 2014 and 2019 – data Dr. Rapoport noted falls in lines with trends in other Western countries, which range between 12% and 13%.

Nearly half of the first-time triptan buyers (43%) did not purchase another triptan for 5 years. In conflict with established guidelines, 90% of patients that discontinued triptan-based treatment had tried only one triptan type.

One important factor contributing to the ease of data collection is that the Danish population has free health care, coupled with sizable reimbursements for their spending. The country’s accessible health care system negates the effects of barriers related to price and availability while engendering data that more accurately reflects the patients’ experience based on treatment need and satisfaction.

“In a cohort with access to free clinical consultations and low medication costs, we observed low rates of triptan adherence, likely due to disappointing efficacy and/or unpleasant side effects rather than economic considerations. Triptan success continues to be hindered by poor implementation of clinical guidelines and high rates of treatment discontinuance,” the researchers concluded.

“The most surprising thing about this study is it is exactly what I would have expected if triptans in the U.S. were free,” Dr. Rapoport said.

Dr. Rapoport is the editor in chief of Neurology Reviews and serves as a consultant to several pharmaceutical companies.

Key clinical point: Propranolol appears more effective in reducing temporomandibular disorder (TMD) pain among migraineurs, with more of the effect mediated by reduced heart rate than by decreased headache impact.

Major finding: Efficacy of propranolol for at least 30% reduction in facial pain index at week 9 was higher among 104 migraineurs (adjusted odds ratio [aOR], 3.3; P = .009; P for treatment group interaction = .139) than 95 non-migraineurs (aOR, 1.3; P = .631; P for treatment group interaction = .139). Only 9% of the treatment effect was mediated by reduced headache, whereas 46% was mediated by reduced heart rate.

Study details: Data come from SOPPRANO, a phase 2b randomized controlled trial that investigated analgesic efficacy of propranolol in 200 patients with chronic myogenous TMD randomly allocated to either propranolol or placebo.

Disclosures: The study was funded by the National Institutes of Health/National Institute of Dental and Craniofacial Research. The authors declared no potential conflicts of interest.

Source: Tchivileva IE et al. Cephalalgia. 2021 Feb 9. doi: 10.1177/0333102421989268.

Key clinical point: Propranolol appears more effective in reducing temporomandibular disorder (TMD) pain among migraineurs, with more of the effect mediated by reduced heart rate than by decreased headache impact.

Major finding: Efficacy of propranolol for at least 30% reduction in facial pain index at week 9 was higher among 104 migraineurs (adjusted odds ratio [aOR], 3.3; P = .009; P for treatment group interaction = .139) than 95 non-migraineurs (aOR, 1.3; P = .631; P for treatment group interaction = .139). Only 9% of the treatment effect was mediated by reduced headache, whereas 46% was mediated by reduced heart rate.

Study details: Data come from SOPPRANO, a phase 2b randomized controlled trial that investigated analgesic efficacy of propranolol in 200 patients with chronic myogenous TMD randomly allocated to either propranolol or placebo.

Disclosures: The study was funded by the National Institutes of Health/National Institute of Dental and Craniofacial Research. The authors declared no potential conflicts of interest.

Source: Tchivileva IE et al. Cephalalgia. 2021 Feb 9. doi: 10.1177/0333102421989268.

Key clinical point: Propranolol appears more effective in reducing temporomandibular disorder (TMD) pain among migraineurs, with more of the effect mediated by reduced heart rate than by decreased headache impact.

Major finding: Efficacy of propranolol for at least 30% reduction in facial pain index at week 9 was higher among 104 migraineurs (adjusted odds ratio [aOR], 3.3; P = .009; P for treatment group interaction = .139) than 95 non-migraineurs (aOR, 1.3; P = .631; P for treatment group interaction = .139). Only 9% of the treatment effect was mediated by reduced headache, whereas 46% was mediated by reduced heart rate.

Study details: Data come from SOPPRANO, a phase 2b randomized controlled trial that investigated analgesic efficacy of propranolol in 200 patients with chronic myogenous TMD randomly allocated to either propranolol or placebo.

Disclosures: The study was funded by the National Institutes of Health/National Institute of Dental and Craniofacial Research. The authors declared no potential conflicts of interest.

Source: Tchivileva IE et al. Cephalalgia. 2021 Feb 9. doi: 10.1177/0333102421989268.

Key clinical point: A 3-month ketogenic diet (KD) resulted in a reduction of painful symptoms of drug refractory chronic migraine.

Major finding: KD significantly reduced the number of migraine days/month from a median of 30 days to 7.5 days (P less than .0001), hours of migraine/day from a median of 24 hours to 5.5 hours (P less than .0016), and pain level at maximum value for 83% of participants that improved for 55% of them (P less than .0024). The median number of drugs taken in a month reduced from 30 to 6 doses.

Study details: This open-label, single-arm clinical trial assessed 38 patients with refractory chronic migraine who adopted a KD for 3 months.

Disclosures: No source of funding was declared. The authors declared no conflicts of interest.

Source: Bongiovanni D et al. Neurol Sci. 2021 Feb 1. doi: 10.1007/s10072-021-05078-5.

Key clinical point: A 3-month ketogenic diet (KD) resulted in a reduction of painful symptoms of drug refractory chronic migraine.

Major finding: KD significantly reduced the number of migraine days/month from a median of 30 days to 7.5 days (P less than .0001), hours of migraine/day from a median of 24 hours to 5.5 hours (P less than .0016), and pain level at maximum value for 83% of participants that improved for 55% of them (P less than .0024). The median number of drugs taken in a month reduced from 30 to 6 doses.

Study details: This open-label, single-arm clinical trial assessed 38 patients with refractory chronic migraine who adopted a KD for 3 months.

Disclosures: No source of funding was declared. The authors declared no conflicts of interest.

Source: Bongiovanni D et al. Neurol Sci. 2021 Feb 1. doi: 10.1007/s10072-021-05078-5.

Key clinical point: A 3-month ketogenic diet (KD) resulted in a reduction of painful symptoms of drug refractory chronic migraine.

Major finding: KD significantly reduced the number of migraine days/month from a median of 30 days to 7.5 days (P less than .0001), hours of migraine/day from a median of 24 hours to 5.5 hours (P less than .0016), and pain level at maximum value for 83% of participants that improved for 55% of them (P less than .0024). The median number of drugs taken in a month reduced from 30 to 6 doses.

Study details: This open-label, single-arm clinical trial assessed 38 patients with refractory chronic migraine who adopted a KD for 3 months.

Disclosures: No source of funding was declared. The authors declared no conflicts of interest.

Source: Bongiovanni D et al. Neurol Sci. 2021 Feb 1. doi: 10.1007/s10072-021-05078-5.

Key clinical point: Galcanezumab reduces the frequency of migraine headache days and may also potentially decrease disabling non-pain symptoms on days when migraine is present in patients with episodic and chronic migraine.

Major finding: Galcanezumab doses of 120 and 240 mg were superior to placebo in reducing the number of monthly migraine days with nausea and/or vomiting in both episodic and chronic migraine studies (all P less than .001). Both doses of galcanezumab were associated with a significant reduction in migraine headache days with photophobia and phonophobia vs. placebo in episodic (P less than .001) and chronic (P less than .001 for galcanezumab 120 mg; P =.001 for galcanezumab 240 mg) migraine studies.

Study details: A post hoc analysis of phase 3 randomized clinical trials EVOLVE-1, EVOLVE-2, and REGAIN that included a total of 2,289 patients with episodic or chronic migraine with or without aura.

Disclosures: This study was funded by Eli Lilly and Company, Indianapolis, IN, USA. K Day, VL Stauffer, V Skljarevski, M Rettiganti, E Pearlman, and SK Aurora reported being current/former full-time employees and/or minor stockholders of Eli Lilly and Company. M Ament reported being a consultant and/or on speaker bureaus for Eli Lilly and Company and others.

Source: Ament M et al. J Headache Pain. 2021 Feb 6. doi: 10.1186/s10194-021-01215-9.

Key clinical point: Galcanezumab reduces the frequency of migraine headache days and may also potentially decrease disabling non-pain symptoms on days when migraine is present in patients with episodic and chronic migraine.

Major finding: Galcanezumab doses of 120 and 240 mg were superior to placebo in reducing the number of monthly migraine days with nausea and/or vomiting in both episodic and chronic migraine studies (all P less than .001). Both doses of galcanezumab were associated with a significant reduction in migraine headache days with photophobia and phonophobia vs. placebo in episodic (P less than .001) and chronic (P less than .001 for galcanezumab 120 mg; P =.001 for galcanezumab 240 mg) migraine studies.

Study details: A post hoc analysis of phase 3 randomized clinical trials EVOLVE-1, EVOLVE-2, and REGAIN that included a total of 2,289 patients with episodic or chronic migraine with or without aura.

Disclosures: This study was funded by Eli Lilly and Company, Indianapolis, IN, USA. K Day, VL Stauffer, V Skljarevski, M Rettiganti, E Pearlman, and SK Aurora reported being current/former full-time employees and/or minor stockholders of Eli Lilly and Company. M Ament reported being a consultant and/or on speaker bureaus for Eli Lilly and Company and others.

Source: Ament M et al. J Headache Pain. 2021 Feb 6. doi: 10.1186/s10194-021-01215-9.

Key clinical point: Galcanezumab reduces the frequency of migraine headache days and may also potentially decrease disabling non-pain symptoms on days when migraine is present in patients with episodic and chronic migraine.

Major finding: Galcanezumab doses of 120 and 240 mg were superior to placebo in reducing the number of monthly migraine days with nausea and/or vomiting in both episodic and chronic migraine studies (all P less than .001). Both doses of galcanezumab were associated with a significant reduction in migraine headache days with photophobia and phonophobia vs. placebo in episodic (P less than .001) and chronic (P less than .001 for galcanezumab 120 mg; P =.001 for galcanezumab 240 mg) migraine studies.

Study details: A post hoc analysis of phase 3 randomized clinical trials EVOLVE-1, EVOLVE-2, and REGAIN that included a total of 2,289 patients with episodic or chronic migraine with or without aura.

Disclosures: This study was funded by Eli Lilly and Company, Indianapolis, IN, USA. K Day, VL Stauffer, V Skljarevski, M Rettiganti, E Pearlman, and SK Aurora reported being current/former full-time employees and/or minor stockholders of Eli Lilly and Company. M Ament reported being a consultant and/or on speaker bureaus for Eli Lilly and Company and others.

Source: Ament M et al. J Headache Pain. 2021 Feb 6. doi: 10.1186/s10194-021-01215-9.

Key clinical point: Lasmiditan is effective in the treatment of an acute migraine attack and demonstrates consistency of response across multiple migraine attacks

Major finding: Lasmiditan doses of 100 and 200 mg were superior to placebo for pain freedom at 2 hours during the first attack (odds ratio [OR], 3.8 and 4.6, respectively; P less than .001) and in at least 2 of 3 attacks (OR, 3.8 and 7.2, respectively; P less than .001). The incidence of severe adverse events was similar across treatment groups.

Study details: Findings are from CENTURION, a phase 3 study that randomly assigned patients with migraine with/without aura to either of 3 treatment groups for 4 attacks: lasmiditan 200 mg (n=536), lasmiditan 100 mg (n=539), or control (n=538).

Disclosures: The CENTURION study was sponsored by Eli Lilly and Company. Some authors including the lead author were full-time employees and minor stockholders at Eli Lilly and Company. Some authors reported receiving speaker fees and honorariums from different sources.

Source: Ashina M et al. Cephalalgia. 2021 Feb 4. doi: 10.1177/0333102421989232.

Key clinical point: Lasmiditan is effective in the treatment of an acute migraine attack and demonstrates consistency of response across multiple migraine attacks

Major finding: Lasmiditan doses of 100 and 200 mg were superior to placebo for pain freedom at 2 hours during the first attack (odds ratio [OR], 3.8 and 4.6, respectively; P less than .001) and in at least 2 of 3 attacks (OR, 3.8 and 7.2, respectively; P less than .001). The incidence of severe adverse events was similar across treatment groups.

Study details: Findings are from CENTURION, a phase 3 study that randomly assigned patients with migraine with/without aura to either of 3 treatment groups for 4 attacks: lasmiditan 200 mg (n=536), lasmiditan 100 mg (n=539), or control (n=538).

Disclosures: The CENTURION study was sponsored by Eli Lilly and Company. Some authors including the lead author were full-time employees and minor stockholders at Eli Lilly and Company. Some authors reported receiving speaker fees and honorariums from different sources.

Source: Ashina M et al. Cephalalgia. 2021 Feb 4. doi: 10.1177/0333102421989232.

Key clinical point: Lasmiditan is effective in the treatment of an acute migraine attack and demonstrates consistency of response across multiple migraine attacks

Major finding: Lasmiditan doses of 100 and 200 mg were superior to placebo for pain freedom at 2 hours during the first attack (odds ratio [OR], 3.8 and 4.6, respectively; P less than .001) and in at least 2 of 3 attacks (OR, 3.8 and 7.2, respectively; P less than .001). The incidence of severe adverse events was similar across treatment groups.

Study details: Findings are from CENTURION, a phase 3 study that randomly assigned patients with migraine with/without aura to either of 3 treatment groups for 4 attacks: lasmiditan 200 mg (n=536), lasmiditan 100 mg (n=539), or control (n=538).

Disclosures: The CENTURION study was sponsored by Eli Lilly and Company. Some authors including the lead author were full-time employees and minor stockholders at Eli Lilly and Company. Some authors reported receiving speaker fees and honorariums from different sources.

Source: Ashina M et al. Cephalalgia. 2021 Feb 4. doi: 10.1177/0333102421989232.

Acute migraine headache attacks

A recent review in the Journal of Neuro-Ophthalmology by Konstantinos Spingos and colleagues (including me as the senior author) details typical and new treatments for migraine. We all know about the longstanding options, including the 7 triptans and ergots, as well as over-the-counter analgesics, which can be combined with caffeine, nonsteroidal anti-inflammatory drugs; and many use the 2 categories of medication that I no longer use for migraine, butalbital-containing medications, and opioids.

Now 2 gepants are available—small molecule calcitonin gene-related peptide (CGRP) receptor antagonists. These medications are thought to be a useful alternative for those in whom triptans do not work or are relatively contraindicated due to coronary and cerebrovascular problems and other cardiac risk factors like obesity, smoking, lack of exercise, high cholesterol, and diabetes. Ubrogepant was approved by the FDA in 2019, and rimegepant soon followed in 2020.

• Ubrogepant: In the ACHIEVE trials, approximately 1 in 5 participants who received the 50 mg dose were pain-free at 2 hours. Moreover, nearly 40% of individuals who received it said their worst migraine symptom was resolved at 2 hours. Pain relief at 2 hours was 59%
• Rimegepant: Like ubrogepant, about 20% of trial participants who received the 75 mg melt tablet dose of rimegepant were pain-free at 2 hours. Thirty-seven percent reported that their worst migraine symptom was gone at 2 hours. Patients began to return to normal functioning in 15 minutes.

In addition to gepants, there is 1 ditan approved, which stimulates 5-HT_1F receptors. Lasmiditan is the first medication in this class to be FDA-approved. It, too, is considered an alternative in patients in whom triptans are ineffective or when patients should not take a vasoconstrictor. In the most recent phase 3 study, the percentage of individuals who received lasmiditan and were pain-free at 2 hours were 28% (50 mg), 31% (100 mg) and 39% (200 mg). Relief from the migraine sufferers’ most bothersome symptom at 2 hours occurred in 41%, 44%, and 49% of patients, respectively. Lasmiditan is a Class V controlled substance. It has 18% dizziness in clinical trials. After administration, patients should not drive for 8 hours, and it should only be used once in a 24-hour period.

Non-pharmaceutical treatment options for acute migraine include nerve stimulation using electrical and magnetic stimulation devices, and behavioral approaches such as biofeedback training and mindfulness.  The Nerivio device for the upper arm is controlled by a smart phone app and seems to work as well as a triptan in some patients with almost no adverse events. Just approved in February is the Relivion device which is worn like a tiara on the head and stimulates the frontal branches of the trigeminal nerve as well as the 2 occipital nerves in the back of the head.

Acute care of cluster headache attacks

In 2011, Ashkenazi and Schwedt published a comprehensive table in Headache outlining the treatment options for acute cluster headache. More recently, a review in CNS Drugs by Brandt and colleagues presented the choices with level 1 evidence for efficacy. They include:

• Sumatriptan, 6 mg subcutaneous injection, or 20 mg nasal spray
• Zolmitriptan, 5 or 10 mg nasal spray
• Oxygen, 100%, 7 to 12 liters per minute via a mask over the nose and mouth

The authors recommend subcutaneous sumatriptan 6 mg and/or high-flow oxygen at 9- to 12- liters per minute for 15 minutes. Subcutaneous sumatriptan, they note, has been shown to achieve pain relief within 15 minutes in 75% of patients who receive it. Moreover, one-third report pain freedom. Oxygen’s efficacy has long been established, and relief comes with no adverse events. As for mask type, though no significant differences have been observed in studies, patients appear to express a preference for the demand valve oxygen type, which allows a high flow rate and is dependent on the user’s breathing rate.

Lidocaine intranasally has been found to be effective when triptans or oxygen do not work, according to a review in The Lancet Neurology by Hoffman and May. The medication is dripped or sprayed into the ipsilateral nostril at a concentration of between 4% and 10%. Pain relief is typically achieved within 10 minutes. This review also reports efficacy with percutaneous vagus nerve stimulation with the gammaCore device and neurostimulation of the sphenopalatine ganglion, though the mechanisms of these approaches are poorly understood. 

Evolving therapies for acute cluster headache include the aforementioned CGRP receptor-antagonists. Additionally, intranasal ketamine hydrochloride is under investigation in an open-label, proof-of-concept study; and a zolmitriptan patch is being evaluated in a double-blind, placebo-controlled trial.

Attacks of migraine occur in 12% of the adult population, 3 times more in women than men and are painful and debilitating. Cluster attacks are even more painful and occur in about 0.1% of the population, somewhat more in men. Both types of headache have a variety of effective treatment as detailed above.

Acute migraine headache attacks

A recent review in the Journal of Neuro-Ophthalmology by Konstantinos Spingos and colleagues (including me as the senior author) details typical and new treatments for migraine. We all know about the longstanding options, including the 7 triptans and ergots, as well as over-the-counter analgesics, which can be combined with caffeine, nonsteroidal anti-inflammatory drugs; and many use the 2 categories of medication that I no longer use for migraine, butalbital-containing medications, and opioids.

Now 2 gepants are available—small molecule calcitonin gene-related peptide (CGRP) receptor antagonists. These medications are thought to be a useful alternative for those in whom triptans do not work or are relatively contraindicated due to coronary and cerebrovascular problems and other cardiac risk factors like obesity, smoking, lack of exercise, high cholesterol, and diabetes. Ubrogepant was approved by the FDA in 2019, and rimegepant soon followed in 2020.

• Ubrogepant: In the ACHIEVE trials, approximately 1 in 5 participants who received the 50 mg dose were pain-free at 2 hours. Moreover, nearly 40% of individuals who received it said their worst migraine symptom was resolved at 2 hours. Pain relief at 2 hours was 59%
• Rimegepant: Like ubrogepant, about 20% of trial participants who received the 75 mg melt tablet dose of rimegepant were pain-free at 2 hours. Thirty-seven percent reported that their worst migraine symptom was gone at 2 hours. Patients began to return to normal functioning in 15 minutes.

In addition to gepants, there is 1 ditan approved, which stimulates 5-HT_1F receptors. Lasmiditan is the first medication in this class to be FDA-approved. It, too, is considered an alternative in patients in whom triptans are ineffective or when patients should not take a vasoconstrictor. In the most recent phase 3 study, the percentage of individuals who received lasmiditan and were pain-free at 2 hours were 28% (50 mg), 31% (100 mg) and 39% (200 mg). Relief from the migraine sufferers’ most bothersome symptom at 2 hours occurred in 41%, 44%, and 49% of patients, respectively. Lasmiditan is a Class V controlled substance. It has 18% dizziness in clinical trials. After administration, patients should not drive for 8 hours, and it should only be used once in a 24-hour period.

Non-pharmaceutical treatment options for acute migraine include nerve stimulation using electrical and magnetic stimulation devices, and behavioral approaches such as biofeedback training and mindfulness.  The Nerivio device for the upper arm is controlled by a smart phone app and seems to work as well as a triptan in some patients with almost no adverse events. Just approved in February is the Relivion device which is worn like a tiara on the head and stimulates the frontal branches of the trigeminal nerve as well as the 2 occipital nerves in the back of the head.

Acute care of cluster headache attacks

In 2011, Ashkenazi and Schwedt published a comprehensive table in Headache outlining the treatment options for acute cluster headache. More recently, a review in CNS Drugs by Brandt and colleagues presented the choices with level 1 evidence for efficacy. They include:

• Sumatriptan, 6 mg subcutaneous injection, or 20 mg nasal spray
• Zolmitriptan, 5 or 10 mg nasal spray
• Oxygen, 100%, 7 to 12 liters per minute via a mask over the nose and mouth

The authors recommend subcutaneous sumatriptan 6 mg and/or high-flow oxygen at 9- to 12- liters per minute for 15 minutes. Subcutaneous sumatriptan, they note, has been shown to achieve pain relief within 15 minutes in 75% of patients who receive it. Moreover, one-third report pain freedom. Oxygen’s efficacy has long been established, and relief comes with no adverse events. As for mask type, though no significant differences have been observed in studies, patients appear to express a preference for the demand valve oxygen type, which allows a high flow rate and is dependent on the user’s breathing rate.

Lidocaine intranasally has been found to be effective when triptans or oxygen do not work, according to a review in The Lancet Neurology by Hoffman and May. The medication is dripped or sprayed into the ipsilateral nostril at a concentration of between 4% and 10%. Pain relief is typically achieved within 10 minutes. This review also reports efficacy with percutaneous vagus nerve stimulation with the gammaCore device and neurostimulation of the sphenopalatine ganglion, though the mechanisms of these approaches are poorly understood. 

Evolving therapies for acute cluster headache include the aforementioned CGRP receptor-antagonists. Additionally, intranasal ketamine hydrochloride is under investigation in an open-label, proof-of-concept study; and a zolmitriptan patch is being evaluated in a double-blind, placebo-controlled trial.

Attacks of migraine occur in 12% of the adult population, 3 times more in women than men and are painful and debilitating. Cluster attacks are even more painful and occur in about 0.1% of the population, somewhat more in men. Both types of headache have a variety of effective treatment as detailed above.

Acute migraine headache attacks

A recent review in the Journal of Neuro-Ophthalmology by Konstantinos Spingos and colleagues (including me as the senior author) details typical and new treatments for migraine. We all know about the longstanding options, including the 7 triptans and ergots, as well as over-the-counter analgesics, which can be combined with caffeine, nonsteroidal anti-inflammatory drugs; and many use the 2 categories of medication that I no longer use for migraine, butalbital-containing medications, and opioids.

Now 2 gepants are available—small molecule calcitonin gene-related peptide (CGRP) receptor antagonists. These medications are thought to be a useful alternative for those in whom triptans do not work or are relatively contraindicated due to coronary and cerebrovascular problems and other cardiac risk factors like obesity, smoking, lack of exercise, high cholesterol, and diabetes. Ubrogepant was approved by the FDA in 2019, and rimegepant soon followed in 2020.

• Ubrogepant: In the ACHIEVE trials, approximately 1 in 5 participants who received the 50 mg dose were pain-free at 2 hours. Moreover, nearly 40% of individuals who received it said their worst migraine symptom was resolved at 2 hours. Pain relief at 2 hours was 59%
• Rimegepant: Like ubrogepant, about 20% of trial participants who received the 75 mg melt tablet dose of rimegepant were pain-free at 2 hours. Thirty-seven percent reported that their worst migraine symptom was gone at 2 hours. Patients began to return to normal functioning in 15 minutes.

In addition to gepants, there is 1 ditan approved, which stimulates 5-HT_1F receptors. Lasmiditan is the first medication in this class to be FDA-approved. It, too, is considered an alternative in patients in whom triptans are ineffective or when patients should not take a vasoconstrictor. In the most recent phase 3 study, the percentage of individuals who received lasmiditan and were pain-free at 2 hours were 28% (50 mg), 31% (100 mg) and 39% (200 mg). Relief from the migraine sufferers’ most bothersome symptom at 2 hours occurred in 41%, 44%, and 49% of patients, respectively. Lasmiditan is a Class V controlled substance. It has 18% dizziness in clinical trials. After administration, patients should not drive for 8 hours, and it should only be used once in a 24-hour period.

Non-pharmaceutical treatment options for acute migraine include nerve stimulation using electrical and magnetic stimulation devices, and behavioral approaches such as biofeedback training and mindfulness.  The Nerivio device for the upper arm is controlled by a smart phone app and seems to work as well as a triptan in some patients with almost no adverse events. Just approved in February is the Relivion device which is worn like a tiara on the head and stimulates the frontal branches of the trigeminal nerve as well as the 2 occipital nerves in the back of the head.

Acute care of cluster headache attacks

In 2011, Ashkenazi and Schwedt published a comprehensive table in Headache outlining the treatment options for acute cluster headache. More recently, a review in CNS Drugs by Brandt and colleagues presented the choices with level 1 evidence for efficacy. They include:

• Sumatriptan, 6 mg subcutaneous injection, or 20 mg nasal spray
• Zolmitriptan, 5 or 10 mg nasal spray
• Oxygen, 100%, 7 to 12 liters per minute via a mask over the nose and mouth

The authors recommend subcutaneous sumatriptan 6 mg and/or high-flow oxygen at 9- to 12- liters per minute for 15 minutes. Subcutaneous sumatriptan, they note, has been shown to achieve pain relief within 15 minutes in 75% of patients who receive it. Moreover, one-third report pain freedom. Oxygen’s efficacy has long been established, and relief comes with no adverse events. As for mask type, though no significant differences have been observed in studies, patients appear to express a preference for the demand valve oxygen type, which allows a high flow rate and is dependent on the user’s breathing rate.

Lidocaine intranasally has been found to be effective when triptans or oxygen do not work, according to a review in The Lancet Neurology by Hoffman and May. The medication is dripped or sprayed into the ipsilateral nostril at a concentration of between 4% and 10%. Pain relief is typically achieved within 10 minutes. This review also reports efficacy with percutaneous vagus nerve stimulation with the gammaCore device and neurostimulation of the sphenopalatine ganglion, though the mechanisms of these approaches are poorly understood. 

Evolving therapies for acute cluster headache include the aforementioned CGRP receptor-antagonists. Additionally, intranasal ketamine hydrochloride is under investigation in an open-label, proof-of-concept study; and a zolmitriptan patch is being evaluated in a double-blind, placebo-controlled trial.

Attacks of migraine occur in 12% of the adult population, 3 times more in women than men and are painful and debilitating. Cluster attacks are even more painful and occur in about 0.1% of the population, somewhat more in men. Both types of headache have a variety of effective treatment as detailed above.

Key clinical point: Treatment with erenumab significantly improved functional outcomes in 3 months in patients with episodic migraine refractory to previous prophylactic therapies.

Major finding: At 12 weeks, erenumab significantly improved “Migraine Physical Function Impact Diary”-“Physical Impairment” and “Everyday Activities” scores compared with placebo (treatment difference [TD], −3.5; P = .003 and TD, −3.9; P less than .001, respectively). A significantly higher proportion of patients had a 5 or more point reduction in the Headache Impact Test score from baseline compared with placebo (odds ratio, 2.4; P = .002).

Study details: Data come from the 12-week, double-blind, multicenter, Liberty study involving 246 episodic migraine patients who did not previously benefit from 2-4 prophylactic treatments. They were randomly assigned to receive either erenumab 140 mg (n = 121) or placebo (n = 125) once every 4 weeks for 12 weeks.

Disclosures: The study was supported by Novartis Pharma AG, Basel, Switzerland. S Wen, P Hours-Zesiger, and J Klatt were employees of, and hold stocks in, Novartis. M Lanteri-Minet, PJ Goadsby, U Reuter, and MD Ferrari reported relationships with various pharmaceutical companies and/or research organizations.

Source:Lanteri-Minet M et al. J Neurol Neurosurg Psychiatry. 2021 Jan 5. doi: 10.1136/jnnp-2020-324396.

Key clinical point: Treatment with erenumab significantly improved functional outcomes in 3 months in patients with episodic migraine refractory to previous prophylactic therapies.

Major finding: At 12 weeks, erenumab significantly improved “Migraine Physical Function Impact Diary”-“Physical Impairment” and “Everyday Activities” scores compared with placebo (treatment difference [TD], −3.5; P = .003 and TD, −3.9; P less than .001, respectively). A significantly higher proportion of patients had a 5 or more point reduction in the Headache Impact Test score from baseline compared with placebo (odds ratio, 2.4; P = .002).

Study details: Data come from the 12-week, double-blind, multicenter, Liberty study involving 246 episodic migraine patients who did not previously benefit from 2-4 prophylactic treatments. They were randomly assigned to receive either erenumab 140 mg (n = 121) or placebo (n = 125) once every 4 weeks for 12 weeks.

Disclosures: The study was supported by Novartis Pharma AG, Basel, Switzerland. S Wen, P Hours-Zesiger, and J Klatt were employees of, and hold stocks in, Novartis. M Lanteri-Minet, PJ Goadsby, U Reuter, and MD Ferrari reported relationships with various pharmaceutical companies and/or research organizations.

Source:Lanteri-Minet M et al. J Neurol Neurosurg Psychiatry. 2021 Jan 5. doi: 10.1136/jnnp-2020-324396.

Key clinical point: Treatment with erenumab significantly improved functional outcomes in 3 months in patients with episodic migraine refractory to previous prophylactic therapies.

Major finding: At 12 weeks, erenumab significantly improved “Migraine Physical Function Impact Diary”-“Physical Impairment” and “Everyday Activities” scores compared with placebo (treatment difference [TD], −3.5; P = .003 and TD, −3.9; P less than .001, respectively). A significantly higher proportion of patients had a 5 or more point reduction in the Headache Impact Test score from baseline compared with placebo (odds ratio, 2.4; P = .002).

Study details: Data come from the 12-week, double-blind, multicenter, Liberty study involving 246 episodic migraine patients who did not previously benefit from 2-4 prophylactic treatments. They were randomly assigned to receive either erenumab 140 mg (n = 121) or placebo (n = 125) once every 4 weeks for 12 weeks.

Disclosures: The study was supported by Novartis Pharma AG, Basel, Switzerland. S Wen, P Hours-Zesiger, and J Klatt were employees of, and hold stocks in, Novartis. M Lanteri-Minet, PJ Goadsby, U Reuter, and MD Ferrari reported relationships with various pharmaceutical companies and/or research organizations.

Source:Lanteri-Minet M et al. J Neurol Neurosurg Psychiatry. 2021 Jan 5. doi: 10.1136/jnnp-2020-324396.